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Tonic activity in inspiratory muscles during continuous negative airway pressure.

We studied tonic inspiratory activity (TIA) induced by continuous negative airway pressure (CNAP) in anaesthetized, spontaneously breathing cats. TIA in the diaphragm and parasternal intercostal muscles (ICM) was quantified in response to tracheal pressure (PTR) = -0.3 to -1.2 kPa. To differentiate between reflexes from rapidly adapting receptors (RARs), slowly adapting receptors (SARs) and C-fiber endings different temperatures of the vagus nerves (TVG) were used between 4 and 37 degrees C. At PTR = -1.2 kPa mean TIA values were 41% and 62% of peak inspiratory EMG activity of control breaths for the diaphragm and ICM, respectively. After vagotomy and for TVG < 6 degrees C CNAP did not induce TIA anymore. Changes in inspiratory and expiratory time during vagal cooling down to 4 degrees C confirmed the selective block of conductance in vagal afferents of the three types of lung receptors. We conclude that CNAP-induced TIA results from stimulation of RARs. Our data strongly indicate that stimulation of SARs suppresses TIA, whereas C-fiber endings are not involved in TIA at all. The results suggest that part of the hyperinflation in bronchial asthma may be caused by TIA in response to mechanical stimulation of RARs.

Airway Resistance↗

Coordination between rib cage muscles and diaphragm during quiet breathing in humans.

The pattern of activation of the scalenes and the parasternal intercostal muscles was studied in relation to the pattern of rib cage and abdominal motion during various respiratory maneuvers in the tidal volume range in five normal humans. Electromyograms (EMG) of the scalenes and parasternal intercostals were recorded with bipolar needle electrodes, and changes in abdominal and rib cage displacement were measured using linearized magnetometers. The scalenes and parasternal intercostals were always active during quiet breathing, and their pattern of activation was identical; in both muscles the EMG activity usually started together with the beginning of inspiration, increased in intensity as inspiration proceeded, and persisted into the early part of expiration. In addition, like the parasternal activity the scalene inspiratory activity persisted until the tidal volume was trivial, increased during tidal inspirations performed with the rib cage alone, and was nearly abolished during diaphragmatic isovolume maneuvers. However, attempts to perform tidal inspiration with the diaphragm alone, while causing an increase in parasternal EMG activity, were associated with a marked reduction or a suppression of scalene EMG activity and a reduced substantially distorted rib cage expansion. In particular, the upper rib cage was then moving paradoxically.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗

Cadaver evaluation of EMG needle insertion techniques used to target muscles of the thorax.

STUDY DESIGN: Measure the accuracy of needle insertion in thoracic muscles of human cadavers. OBJECTIVES: Evaluate the effectiveness of known EMG techniques for sampling thoracic innervated muscles. SUMMARY OF BACKGROUND DATA: The evaluation of thoracic radiculopathies requires accurate electrodiagnostic techniques for evaluating the thoracic myotomes. METHODS: An American Board of Electrodiagnostic Medicine certified physician placed needles into pertinent muscles of the thorax and an anatomist serving as a blinded dissector recorded the path and accuracy of needle. RESULTS: Needle examination of thoracic muscles was as accurate as limb needle examination. No notable risks are noted in multifidus sampling. However, in the cadaver, some risks were noted in association with placements in the intercostal muscles. The target muscle was reliably sampled, but the rib or vertebral level was difficult to landmark in the cadaver. CONCLUSIONS: Needle examination of the thoracic multifidus and intercostals is reliable, although further confirmation is needed to accurately verify the appropriate vertebral or rib level being sampled.

Adult↗

Intracellular free [Ca2+] in human skeletal muscle with myopathic carnitine deficiency.

Carnitine is required for the transport of activated long chain fatty acids through the mitochondrial inner membrane. We measured the intracellular free calcium concentration [( Ca2+]i) by means of a calcium selective microelectrode in skeletal muscle biopsies obtained from nine patients in which myopathic carnitine deficiency (MCD) was diagnosed, and from six subjects with no evidence of neuromuscular disease. Intact intercostal muscle bundles were dissected and then split for electron microscopic studies and electrophysiological measurements. The [Ca2+]i in muscle fibers from MCD patients was 0.46 +/- 0.02 mumol.l-1 (mean +/- SEM) and 0.10 +/- 0.01 mumol.l-1 in control subjects. At the electron microscopic level, the predominant abnormality was the presence of lipid vacuoles between the myofibrils. These results show that in patients with myopathic carnitine deficiency there is a significant increase in the resting myoplasmic calcium concentration which might be related to a malfunction of some mechanisms responsible for the homeostasis of intracellular calcium.

Adolescent↗

Experimental infection with Taenia saginata (Poland strain) in Taiwanese pigs.

Two 22-day-old Landrace-Small Ear Miniature (L-SEM) pigs, five 45 to 66-day-old Small Ear Miniature (SEM) pigs, and one 16-day-old Holstein calf were each fed 1000, 3000 or 10,000 Taenia saginata (Poland strain) eggs respectively and killed 34-77 days after inoculation. Four of the five SEM pigs and the Holstein calf were susceptible to this parasite. However, two L-SEM pigs and one SEM pig remained negative. The cysticerci recovery rates for the SEM pig and Holstein calf were 36% and 3%, respectively. All cysticerci from the SEM pigs were found in the livers, more in the parenchyma (89%) than on the surface (11%). Only eleven cysticerci in two SEM pigs were mature and the remainder were either immature, degenerated or calcified. The cysticerci in the calf were distributed throughout the body: leg muscles (248), heart (27), tongue (17), intercostal muscles (14), diaphragm (5), kidney (1) and liver (1). Most (299) of the cysticerci were mature, one was immature and 13 were degenerated or calcified. The length, width, diameter of the protoscolex and sucker of the cysticerci from the calf were larger than those from the SEM pigs. However, the diameter of the rostellum of the latter was slightly larger than the former. Hooklets were not found on any mature cysticercus recovered. The results of the present study provide evidence that the SEM pig can be used as an experimental intermediate host for T. saginata.

Animals↗

Distinct regulatory elements control muscle-specific, fiber-type-selective, and axially graded expression of a myosin light-chain gene in transgenic mice.

The fast alkali myosin light chain 1f/3f (MLC1f/3f) gene is developmentally regulated, muscle specific, and preferentially expressed in fast-twitch fibers. A transgene containing an MLC1f promoter plus a downstream enhancer replicates this pattern of expression in transgenic mice. Unexpectedly, this transgene is also expressed in a striking (approximately 100-fold) rostrocaudal gradient in axial muscles (reviewed by J. R. Sanes, M. J. Donoghue, M. C. Wallace, and J. P. Merlie, Cold Spring Harbor Symp. Quant. Biol. 57:451-460, 1992). Here, we analyzed the expression of mutated transgenes to map sites necessary for muscle-specific, fiber-type-selective, and axially graded expression. We show that two E boxes (myogenic factor binding sites), a homeodomain (hox) protein binding site, and an MEF2 site, which are clustered in an approximately 170-bp core enhancer, are all necessary for maximal transgene activity in muscle but not for fiber-type- or position-dependent expression. A distinct region within the core enhancer promotes selective expression of the transgene in fast-twitch muscles. Sequences that flank the core enhancer are also necessary for high-level activity in transgenic mice but have little influence on activity in transfected cells, suggesting the presence of regions resembling matrix attachment sites. Truncations of the MLC1f promoter affected position-dependent expression of the transgene, revealing distinct regions that repress transgene activity in neck muscles and promote differential expression among intercostal muscles. Thus, the whole-body gradient of expression displayed by the complete transgene may reflect the integrated activities of discrete elements that regulate expression in subsets of muscles. Finally, we show that transgene activity is not significantly affected by deletion or overexpression of the myoD gene, suggesting that intermuscular differences in myogenic factor levels do not affect patterns of transgene expression. Together, our results provide evidence for at least nine distinct sites that exert major effects on the levels and patterns of MLC1f expression in adult muscles.

Animals↗

Pulmonary function and maximal transrespiratory pressures in ankylosing spondylitis.

Clinical measurements and pulmonary functions, including maximal transrespiratory pressures, were studied in 30 patients (age 43 (SD 10) years) with ankylosing spondylitis. Vital capacity (VC) was slightly reduced to 79 (16)% and forced expiratory volume in one second (FEV1) was similarly reduced to 82 (20)% such that the average FEV1/VC ratio was 77.8 (6.65). Total lung capacity was slightly reduced to 85 (13)%. Transfer factor of the lung for carbon monoxide (TLCO) averaged 88 (17)% and TLCO per unit lung volume was 114 (26)%. Reductions in lung volumes correlated well with clinical measurements. Both maximal expiratory pressures (PEmax) and inspiratory pressures (PImax) were clearly reduced to 56 (17)% and 76 (28)% respectively. This suggests that spirometrically determined volumes were better preserved than respiratory muscle strength in ankylosing spondylitis. It is speculated that the reduction in respiratory muscle strength may be due to intercostal muscle atrophy.

Adult↗

Coordination of intrinsic and extrinsic tongue muscles during spontaneous breathing in the rat.

The muscular-hydrostat model of tongue function proposes a constant interaction of extrinsic (external bony attachment, insertion into base of tongue) and intrinsic (origin and insertion within the tongue) tongue muscles in all tongue movements (Kier WM and Smith KK. Zool J Linn Soc 83: 207-324, 1985). Yet, research that examines the respiratory-related effects of tongue function in mammals continues to focus almost exclusively on the respiratory control and function of the extrinsic tongue protrusor muscle, the genioglossus muscle. The respiratory control and function of the intrinsic tongue muscles are unknown. Our purpose was to determine whether intrinsic tongue muscles have a respiration-related activity pattern and whether intrinsic tongue muscles are coactivated with extrinsic tongue muscles in response to respiratory-related sensory stimuli. Esophageal pressure and electromyographic (EMG) activity of an extrinsic tongue muscle (hyoglossus), an intrinsic tongue muscle (superior longitudinal), and an external intercostal muscle were studied in anesthetized, tracheotomized, spontaneously breathing rats. Mean inspiratory EMG activity was compared at five levels of inspired CO2. Intrinsic tongue muscles were often quiescent during eupnea but active during hypercapnia, whereas extrinsic tongue muscles were active in both eupnea and hypercapnia. During hypercapnia, the activities of the airway muscles were largely coincident, although the onset of extrinsic muscle activity generally preceded the onset of intrinsic muscle activation. Our findings provide evidence, in an in vivo rodent preparation, of respiratory modulation of motoneurons supplying intrinsic tongue muscles. Distinctions noted between intrinsic and extrinsic activities could be due to differences in motoneuron properties or the central, respiration-related control of each motoneuron population.

Animals↗

Evaluation of a respiratory muscle biofeedback procedure-effects on heart rate and dyspnea.

Patients with respiratory diseases or anxiety frequently complain about dyspnea, which may be partly related to chronic tension of respiratory muscles and/or dynamic hyperinflation. In two experiments we tested a biofeedback technique that recorded electromyographic (EMG) activity from a bipolar surface electrode placement over the right external intercostal muscles with visual signal feedback. Healthy participants were tested in their ability to alter the signal. Heart rate was measured continuously throughout training trials. In the second experiment, dyspnea was rated on a modified Borg scale after each trial. Participants were able to increase their EMG activity considerably while heart rate and dyspnea increased substantially. Changes in EMG activity were achieved mostly by manipulating accessory muscle tension and/or altering breathing pattern. Thus, the technique is capable of altering respiratory muscle tension and associated dyspnea. Further studies may test the procedure as a relaxation technique in patients with respiratory disease or anxiety.

Adult↗

Mechanism of rib cage inspiratory muscle recruitment in diaphragmatic paralysis.

Paralysis of the diaphragm promotes an increase in the activation of the rib cage inspiratory muscles, and previous studies have suggested that this compensation is primarily due to vagal mechanisms (6). To test this hypothesis, we have assessed the effect of diaphragmatic paralysis on the electrical response of 19 parasternal intercostal muscles in eight anesthetized, vagotomized, spontaneously breathing dogs in the supine posture. Complete diaphragmatic paralysis was induced by section of the C5, C6, and C7 phrenic nerve roots in the neck. With the animals breathing room air, diaphragmatic paralysis resulted in a mean 94% increase in the peak height of integrated parasternal activity (p less than 0.001) associated with a 14 mm Hg decrease in arterial PO2 (p less than 0.05) and an 8 mm Hg increase in arterial PCO2 (p less than 0.001). The augmented parasternal activity was unrelated to the duration of inspiration and persisted when the animals were given a hyperoxic gas mixture. Thus the rib cage inspiratory muscles still compensate for diaphragmatic paralysis in the absence of vagal signals and of hypoxemia. This compensation probably results from the considerably augmented CO2 load placed on the extradiaphragmatic muscles.

Animals↗

Comparison of Ca(2+) sparks produced independently by two ryanodine receptor isoforms (type 1 or type 3).

The molecular determinants of a Ca(2+) spark, those events that determine the sudden opening and closing of a small number of ryanodine receptor (RyR) channels limiting Ca(2+) release to a few milliseconds, are unknown. As a first step we investigated which of two RyR isoforms present in mammalian embryonic skeletal muscle, RyR type 1(RyR-1) or RyR type 3 (RyR-3) has the ability to generate Ca(2+) sparks. Their separate contributions were investigated in intercostal muscle cells of RyR-1 null and RyR-3 null mouse embryos. A comparison of Ca(2+) spark parameters of RyR-1 null versus RyR-3 null cells measured at rest with fluo-3 showed that neither the peak fluorescence intensity (DeltaF/F(o) = 1.25 +/- 0.7 vs. 1.55 +/- 0.6), spatial width at half-max intensity (FWHM = 2.7 +/- 1.2 vs. 2.6 +/- 0.6 microm), nor the duration at half-max intensity (FTHM = 45 +/- 49 vs. 43 +/- 25 ms) was significantly different. Sensitivity to caffeine (0.1 mM) was remarkably different, with sparks in RyR-1 null myotubes becoming brighter and longer in duration, whereas those in RyR-3 null cells remained unchanged. Controls performed in double RyR-1/RyR-3 null cells obtained by mice breeding showed that sparks were not observed in the absence of both isoforms in >150 cells imaged. In conclusion, 1) RyR-1 and RyR-3 appear to be the only intracellular Ca(2+) channels that participate in Ca(2+) spark activity in embryonic skeletal muscle; 2) except in their responsiveness to caffeine, both isoforms have the ability to produce Ca(2+) sparks with nearly identical properties, so it is rather unlikely that a single RyR isoform, when others are also present, would be responsible for Ca(2+) sparks; and 3) because RyR-1 null cells are excitation-contraction (EC) uncoupled and RyR-3 null cells exhibit a normal phenotype, Ca(2+) sparks result from the inherent activity of small clusters of RyRs regardless of the participation of these RyRs in EC coupling.

Animals↗

Medullary inspiratory activity: influence of intercostal tendon organs and muscle spindle endings.

Studies were conducted to determine the effects of intercostal muscle spindle endings (MSEs) and tendon organs (TOs) on medullary inspiratory activity in decerebrate and allobarbital-anesthetized cats. Impeded muscle contractions, elicited by electrical stimulation of the peripheral cut end of the T6 ventral root, were used to stimulate external and internal intercostal TOs without MSEs. Impeded contractions of either the external or internal intercostal muscles reduced phrenic and medullary inspiratory neuronal activities. Vibration was used to selectively stimulate external or internal intercostal MSEs (90 and 40 micron amplitude, respectively). Selective stimulation of either external or internal intercostal MSEs did not change phrenic or medullary inspiratory neuronal activities. It is concluded that both external and internal intercostal TOs have a generalized inhibitory effect on medullary inspiratory activity and intercostal MSEs have no effect on medullary inspiratory activity.

Animals↗

Inhomogeneous activation of the parasternal intercostals during breathing.

Recent computations of the mechanical advantage of the canine intercostal muscles have suggested that the inspiratory advantage of the parasternal intercostals is not uniform. In the present studies, we have initially tested this hypothesis. Using a caliper and markers implanted in the costal cartilages, we have thus measured, in four supine paralyzed dogs, the length of the medial, middle, and lateral parasternal fibers at functional residual capacity and after a 1-liter mechanical inflation. With inflation, the medial fibers always shortened more than did the middle fibers (-9.8 +/- 0.8 vs. -6.0 +/- 0.8%; P < 0.001), whereas the lateral fibers remained virtually constant in length (-0.2 +/- 0.8%). This gradient of mechanical advantage agreed well with the gradient of orientation of the muscle fibers. Therefore, we have also recorded the electromyograms of the medial, middle, and lateral parasternal bundles during spontaneous breathing in nine anesthetized animals (20 interspaces); each activity was expressed as a percentage of the activity recorded during tetanic, supramaximal stimulation of the internal intercostal nerve (maximal activity). The medial bundle was invariably more active than was the middle bundle during resting breathing (57.3 +/- 3.3 vs. 25.5 +/- 3.4% of maximum; P < 0.001), and in 10 interspaces, medial activity consistently preceded middle activity at the onset of inspiration. These differences persisted during hypercapnia, during inspiratory resistive loading, as well as after phrenicotomy. Activity was never recorded from the lateral bundle.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

[Effects of midazolam on respiratory drive in healthy volunteers].

OBJECTIVE: To compare the effects of a sedative dose of midazolam on mean inspiratory flow (VT/TI = index of central respiratory activity), known as being decreased by midazolam and the intercostal muscle activity, known as being increased by this agent. STUDY DESIGN: Laboratory study. PATIENTS: Seven healthy volunteers. METHODS: After assessment of baseline values of ventilatory variables and intercostal electromyographic activity (in arbitrary units), midazolam 0.1 mg.kg-1 was administered by iv route. The measurements were repeated after 5 and 10 min, and finally 2 min after the i.v. injection of flumazenil 1 mg. RESULTS: Midazolam decreased VE and VT. Similarly VT/TI ratio decreased from 0.44 +/- 0.04 (baseline value) to 0.26 +/- 0.03 (5 min) and 0.3 +/- 0.03 L.s-1 (10 min later) respectively (P < 0.05). Conversely, midazolam increased the intercostal electromyographic activity from 4.0 +/- 0.7 (baseline value) to 26.5 +/- 16.6 (5 min) and 28.4 +/- 16.6 U (10 min later) respectively (P < 0.05). Within 2 min after flumazenil administration all variables returned to baseline values. CONCLUSIONS: The decrease of VT/TI ratio is probably linked to increased resistances in the upper airways. This ratio cannot act as an indicator of respiratory drive during sedation or anaesthesia. The assessment of the ventilatory effects of benzodiazepines must be based simultaneously of the various other indicators of the ventilatory drive, as these agents act on the different stages of the ventilatory cycle and therefore cannot be characterized by a unique variable.

Adjuvants, Anesthesia↗

Inspiratory elevation of the ribs in the dog: primary role of the parasternals.

To assess the relative contributions of the different groups of inspiratory intercostal muscles to the cranial motion of the ribs in the dog, we have measured the axial displacement of the fourth rib and recorded the electromyograms of the parasternal intercostal, external intercostal, and levator costae in the third interspace in 15 anesthetized animals breathing at rest. In eight animals, the parasternal intercostals were denervated in interspaces 1-5. This procedure caused a marked increase in the amount of external intercostal and levator costae inspiratory activity, and yet the inspiratory cranial motion of the rib was reduced by 55%. On the other hand, the external intercostals in interspaces 1-5 were sectioned in seven animals, and the reduction in the cranial rib motion was only 22%; the amount of parasternal and levator costae activity, however, was unchanged. When the parasternals in these animals were subsequently denervated, the levator costae inspiratory activity increased markedly, but the inspiratory cranial motion of the rib was abolished or reversed into an inspiratory caudal motion. These studies thus confirm that, in the dog breathing at rest, the parasternal intercostals have a larger role than the external intercostals and levator costae in causing the cranial motion of the ribs during inspiration. A quantitative analysis suggests that the parasternal contribution is approximately 80%.

Animals↗

Pulmonary resistance and compliance changes evoked by pulmonary opiate receptor stimulation.

The administration of [D-Ala2,Met5]enkephalinamide (DAME, 10-250 micrograms/kg) or morphine sulfate (MS, 2 mg/kg) into the right atrium (RA) of spontaneously breathing decerebrate rats caused an increase in lung resistance (RL) and a decrease in dynamic compliance (Cdyn). The maximal percentage increase in RL for DAME (250 micrograms/kg) and MS (2 mg/kg) was 120 +/- 21 and 160 +/- 40%, respectively, occurring during the first 30 s following an initial period of apnea, and subsiding within 1.5-2.0 min. The fall in Cdyn (DAME = -31 +/- 8%; MS = -35 +/- 4%) followed a more prolonged time course returning to control within 4-5 min. These responses were completely abolished by pretreatment with naloxone HCl (100 micrograms/kg i.v.), as well as bilateral cervical vagotomy. Pretreatment with antihistaminic, antiserotinergic, and antimuscarinic agents had no effect on the opioid induced changes in RL and Cdyn. Further studies carried out in ventilated animals showed blockade of the mechanical responses following the administration of neuromuscular blockers, C7 spinal cord transection, and ventral midline opening and retraction of the chest. Electromyograms obtained from intercostal muscles showed excitation of expiratory motor units and inhibition of inspiratory motor units following the administration of opioids. Similar results were obtained with phenyldiguanide (PDG), a known stimulant of pulmonary J-receptors. However, PDG effects were not blocked by naloxone. It was concluded that changes in RL resulted from a decrease in thoracic volume and resultant decrease in the radial traction of the airways. Changes in Cdyn were caused by spasm of expiratory muscles of the chest wall.

Animals↗

Relationship of thoracic volume and airway occlusion pressure: muscular effects.

The occluded airway pressure generated by contraction of inspiratory muscles was measured in spontaneously breathing, anesthetized, vagotomized cats at thoracic volumes below, at, and above true FRC (range, -8 to +28 ml/kg). A relatively constant neural drive at all volumes was shown by recordings of integrated phrenic nerve and external intercostal muscle activities. Peak occlusion pressure declined progressively with increasing thoracic volume and increased with occlusion volumes below FRC. Occlusion pressures measured early in inspiration (0.3 and 0.5 s) decreased similarly. Since occluded airway pressure was a satisfactory index of muscle force output of all inspiratory muscles, the study demonstrates that inspiratory muscle performance decreases with increasing thoracic volume throughout the range studied. Analysis of all occluded breaths shows that, quantitatively, the decline in muscle performance from that occurring at true FRC was -1.9% per ml/kg volume change from FRC. Zero effective muscle pressure generation occurred at 52 ml/kg above FRC, or 2.8 times FRC. These findings have important implications for the use of occlusion pressures and ventilatory responses in respiratory control system studies, since changes in FRC may affect muscle performance.

Airway Obstruction↗

Action of human respiratory muscles inferred from finite element analysis of rib cage.

The actions of several human respiratory muscles have been inferred from finite element analysis of the rib cage. The human model is based on anatomic and mechanical measurements in dogs and human cadavers. As in an earlier canine model, the external and internal (interosseous) intercostal muscles were found to cause, respectively, inspiratory and expiratory displacements of the rib cage, in agreement with the two-dimensional geometric analysis of Hamberger. When extended to three dimensions, Hamberger's analysis helps explain why muscles at the side of the rib cage produce changes in the anteroposterior diameter, whereas muscles at the front and back of the rib cage cause changes in the transverse diameter.

Humans↗